Liver cancer (hepatocellular carcinoma)

Hepatocellular carcinoma (HCC, liver cancer) is the third most common cause of
cancer-related death in the world. Furthermore, the incidence of this cancer
appears to be increasing – in the United Kingdom there were 1.4 new diagnoses
of HCC per 100,000 people in 1975, but this rose to an incidence of 3.9 new
diagnoses per 100,000 people in 2006.

In 80-90% of cases, HCC develops in patients with underlying chronic liver
disease (cirrhosis) (see picture 1). Worldwide, a patient with cirrhosis is more
likely to die as a result of HCC than as a result of any other liver-related
complication.

(picture 1, liver cirrhosis with hepatocellular carcinoma)

Chronic infection with the viruses hepatitis B and hepatitis C is the most
common underlying cause of liver disease that predisposes to HCC, although HCC
can develop in patients with liver disease due to any cause. Another wellrecognised
risk factor for HCC is a poison produced by the fungus Aspergillus.
This fungus contaminated grain in West Africa and China, and if eaten by
patients with Hepatitis B, it increases their risk of developing HCC by 5 times.

Lastly, liver disease due to alcohol and due to ‘fatty liver’ (an increasingly
common cause of liver disease seen in people who do not drink alcohol but who
are overweight, or have diabetes, high cholesterol or high blood pressure), is also
a recognised risk factor for HCC, and this is particularly the case in the Western
World where the prevalence of obesity and diabetes has increased significantly
over the past decade.

Unfortunately, HCC usually presents late – in other words, patients can have no
symptoms until the cancer is already advanced. It is usually diagnosed on the
basis of a blood test called the alpha-fetoprotein, which is elevated in most
people with HCC, and a lesion seen within the liver on ultrasound or computed
tomography (CT) scanning (see picture 2). The outcome from this type of cancer
is therefore poor; one study found an average survival of 17 months in 102
patients with cirrhosis and HCC. Furthermore, the cancer can grow rapidly,
doubling in size over a period of between one month and one year. However,
patients who are detected with early HCC (such as a single, small cancer and with
liver disease that is still stable) have a much better outcome and are, for
example, more likely to be able to undergo surgery for their cancer.(

(picture 2, CT scan showing hepatocellular carcinoma, arrow)

Therefore, in all patients with cirrhosis, it is recommended that regular blood
tests and scans are performed every 6 months (even if the patient is well) in
order to attempt to diagnose the HCC when it is still at a relatively early stage.
This ‘screening’ approach has been shown to save lives in a large trial in China.
This approach has also been shown to be cost-effective in the UK.

Various treatment options are available for patients diagnosed with HCC. In
those who present with an early cancer, curative surgery may be possible in the
form of resection of part of the liver or a liver transplant (see picture 3). This
results in a more than 50% chance of surviving more than 5 years, although the
cancer can recur. Otherwise, treatment with chemotherapy or locally
destructive treatments may be offered, but these treatments would not result in
a cure. New treatments are also emerging but at present these are largely
experimental.

(picture 3, liver transplant scar)

The only way to prevent the development of this cancer would be by diagnosing
the underlying liver condition at an earlier stage and attempting to treat the liver
condition before it progresses to cirrhosis. For example, vaccination against the
hepatitis B virus is offered to the entire population in countries where the
prevalence of the virus is high (for example, Taiwan), and to people at high-risk
of getting infected with the virus in other countries (for example, the vaccine is
provided to all babies born to hepatitis B-positive mothers in the UK).

For patients with known liver disease (from whatever cause), treatment should
be offered for the underlying cause of the liver disease (for example, antiviral
therapy in patients with hepatitis B or hepatitis C). Furthermore, patients with
cirrhosis should be identified as early as possible, so that they can be entered
into a screening programme to detect an HCC at an early stage, when curative
therapy may still be an option.

Currently, the identification of cirrhosis can only reliably be established by
performing a liver biopsy. This involves removing a small sample of the liver
using a special needle, and is performed under local anaesthetic. The sample is
then analysed under the microscope to make a histological diagnosis of cirrhosis.
A liver biopsy does carry a small but significant risk of complications (such as
bleeding, the need for surgery and even death). Therefore, newer, non-invasive
techniques are being evaluated that may permit the diagnosis of cirrhosis
without the need for a liver biopsy. These techniques include specialised blood
tests (called fibrosis markers) and a scan that measures the stiffness of the liver.
This technique is called transient elastography and the scan involved is called a
Fibroscan (see picture 4). The level of liver stiffness correlates well with the
degree of liver damage and therefore allows a diagnosis of fibrosis or cirrhosis to
be made with a high degree of confidence and without need for a liver biopsy.

(picture 4, Fibroscan machine in use)

In summary, HCC is a leading cause of death worldwide and cirrhosis is the main
risk factor. Prevention of cirrhosis would greatly reduce the incidence of this
cancer. Early diagnosis of this cancer through screening of patients with
cirrhosis has been shown to be cost-effective, and may result in a curative option.
Newer, experimental treatments are emerging.